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Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao de-en xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling Shi Quan-Hong Ma department of Neurology and Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and proteostasis.In this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements.We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases.In summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders.This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

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Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation

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Chinese Journal of Integrative Medicine 2024年第7期30卷 600-607页

作者： xu Ben ZHANG Jia-en YE Lin YUAN Chang-wei department of Urology Peking University First Hospital and Institute of Urology Peking UniversityNational Urological Cancer Center

Objective: To explore the molecular mechanism by which curcumin affects renal interstitial fibrosis（RIF） progression by regulating ADAM metallopeptidase with thrombospondin type 1 motif 18（ADAMTS18） methylation. Methods: NRK-49F cells RIF model were induced with transforming growth factor β1（TGF-β1）. Effects of different concentrations of curcumin（0, 10, 20, and 30 μmol/L） on cell proliferation, cell cycle, cell apoptosis as well as cyclin D1 expression were analyzed by cell counting kit-8, flow cytometry and Western blot, respectively. ADAMTS18 methylation levels were determined by methylation-specific polymerase chain reaction. ADAMTS18, fibronectin（FN）, type Ⅰ collagen（Col-Ⅰ） and alpha-smooth muscle actin（α-SMA） mRNA and protein expressions were analyzed by real-time PCR（RT-PCR） and Western blot, respectively. Meanwhile, cells were treated with 50 mmol/L 5-aza-2'-deoxycytidine（5-aza-dC, demethylation agent） for 72 h. Effect of curcumin on extracellular matrix（ECM） deposition was evaluated by immunochemical staining and Western blot. NRK-49F cells were transfected with ADAMTS18 small interfering RNA and grouped into a normal control, ADAMTS18-knock-out（KO）, and ADAMTS18-KO+ 30 μmol/L curcumin groups, and whether curcumin can reverse the effect of ADAMTS18 knockdown on RIF was evaluated. Results: Compared with the control group, TGF-β1 significantly inhibited the proliferation of NRK-49F cells, blocked the G1/G0phase, promoted cell apoptosis and inhibited cyclin D1 expression（Pent concentrations of curcumin, 30 μmol/L curcumin significantly reversed these processes（Pdeposition of FN, Col-Ⅰ and α-SMA（Pdeposition. ADAMTS18 knockdown promoted ECM accumulation, and curcumin reversed this process（P<0.01）. Conclusion: TGF-β1 induced fibrosis in NRK-49F cells.

关键词： renal fibrosis curcumin Chinese medicine ADAMTS18 methylation modification

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Melt flow,heat transfer and solidification in a flexible thin slab continuous casting mold with vertical-combined electromagnetic braking

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Journal of Iron and Steel Research(International) 2024年第2期31卷 401-415页

作者： Lin xu Ze-feng Han Christian Karcher en-gang Wang Key Laboratory of Electromagnetic Processing of Materials(Ministry of Education) Northeastern UniversityShenyang110819LiaoningChina Key Laboratory of Liaoning Province for Clean Combustion Power Generation and Heating Technology Shenyang Institute of EngineeringShenyang110136LiaoningChina Institute of Thermodynamics and Fluid Mechanics Technische Universität IlmenauIlmenau98684Germany

During continuous casting of steel slabs,the application of electromagnetic braking technology(EMBr)provides an effective tool to influence solidification by controlling the pattern of melt flow in the mold.Thus,the quality of the final product can be improved considerably.A new electromagnetic braking(EMBr)method,named vertical-combined electromagnetic braking(VC-EMBr),is proposed to be applied to a flexible thin slab casting(FTSC)mold.To evaluate the beneficial effects of the VC-EMBr,the melt flow,heat transfer,and solidification processes in the FTSC mold are studied by means of numerical simulations.In detail,a Reynolds-averaged Navier–Stokes turbulence model together with an enthalpy-porosity approach was used.The numerical findings are compared with respective simulations using the traditional Ruler-EMBr.The results demonstrate that the application of the VC-EMBr contributes significantly to preventing relative slab defects.In contrast to the Ruler-EMBr,the additional vertical magnetic poles of the VC-EMBr preferentially suppress the direct impact of jet flow on the narrow face of FSTC mold and considerably diminish the level fluctuation near the meniscus region.For instance,by applying a magnetic flux density of 0.3 T,the maximum amplitude of meniscus deflection reduces by about 80%.Moreover,the braking effect of the VC-EMBr effectively improves the homogeneity of temperature distribution in the upper recirculation region and increases the solidified shell thickness along the casting direction.On this basis,the newly proposed VC-EMBr shows a beneficial effect in preventing relative slab defects for FTSC thin slab continuous casting.

关键词： Electromagnetic braking Mold Melt flow Heat transfer Solidification

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Immediate implantation of ultrafine fiber slow-release system based on cell electrospinning to induce osteogenesis of mesenchymal stem cells

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Regenerative Biomaterials 2024年第2期3卷 76-87页

作者： Tao Lu Long Yang Zhuoyang Li Yin Liu Shun'en xu Chuan Ye department of Orthopaedics The Affliated Hospital of Guizhou Medical UniversityGuiyang 550004China department of Orthopaedics The First People's Hospital of GuiyangGuiyang 550004China Center for Tissue engineering and Stem Cell Research Guizhou Medical UniversityGuiyang 550004China department of Otolaryngology Head and Neck Surgery Xinqiao HospitalArmy Medical University(Third Military Medical University)Chongqing 400037China department of dental implant Stomatological Hospital of GuiyangGuiyang 550000China

This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(P34HB)ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells(HUCMSCs).Utilizing dual-nozzle and cell electrospinning techniques,the system encapsulates L-ascorbic acid-2-phosphate magnesium(AsP),βB-glycerophosphate sodium and dexamethasone(deX)within the'fbers,ensuring sustained osteogenic differentiation.The scaffold's morphology,characterization,hydrophilicity,mechanical properties and cellular behavior were examined.Immediate subcutaneous implantation in rabbits was con-ducted to observe its ectopic osteogenic induction effect.Successfully fabricated P34HB ultrafine fiber slow-release sys-tem.Charact ization med.theuniform distribution of HUCMSCs and inducing components within the scaffold,with no chemical reactions affecting the active components.In vitro tests showcased a prolonged release of deX and ASP,while biocompatibility assays highlighted the scaffold's suitability for cellular growth.Alizarin Red,type I collagen,and osteopontin(OPN)staining verifed the scaffold's potent osteogenic induction effect on HUCMsCs.Notably,immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 weeks.These findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction,marking a promising advancement in bone tissue engineering.

关键词： bone tissue engineering cell electrospinning in vivo induction immediate implantation biomaterials

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The Perturbed Compound Poisson Risk Model with Proportional Investment

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Acta Mathematicae Applicatae Sinica 2024年第1期40卷 109-128页

作者： Nai-dan deng Chun-wei Wang Jia-en xu School of Mathematics and Statistics Henan University of Science and TechnologyLuoyang471023China

In this paper, the insurance company considers venture capital and risk-free investment in a constant proportion. The surplus process is perturbed by diffusion. At first, the integro-differential equations satisfied by the expected discounted dividend payments and the Gerber-Shiu function are derived. Then, the approximate solutions of the integro-differential equations are obtained through the sinc method. Finally, the numerical examples are given when the claim sizes follow different distributions. Furthermore, the errors between the explicit solution and the numerical solution are discussed in a special case.

关键词： expected discounted dividend payments lognormal distribution proportional investment perturbed risk model sinc numerical method

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Troy: Efficient Service deployment for Windows Systems

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Chinese Journal of Electronics 2024年第1期33卷 313-322页

作者： deyu ZHANG Yu XIE Mucong xu en CHenG Xiaoyan KUI Bangwen HE Yunhao LI School of Computer Science and engineering Central South University

The modern university computer lab and kindergarden through 12th grade classrooms require a centralized solution to efficiently manage a large number of desktops. The existing solutions either bring virtualization overhead in runtime or requires loading a large image over 30 GB leading to an unacceptable network latency. In this work, we propose Troy which takes advantage of the differencing virtual hard disk techniques in Windows systems.As such, Troy only loads the modifications made on one machine to all other machines. Troy consists of two modules that are responsible to generate an initial image and merge a differencing image with its parent image, respectively. Specifically, we identify the key fields in the virtual hard disk image that links the differencing image and the parent image and find the modified blocks in the differencing images that should be used to replace the blocks in the parent image. We further design a lazy copy solution to reduce the I/O burden in image merging. We have implemented Troy on bare metal machines. The evaluation results show that the performance of Troy is comparable to the native implementation in Windows, without requiring the Windows environment.

关键词： Service deployment Virtual hard disk File system merging Windows system

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Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance

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中华医学杂志(英文版) 2024年第7期137卷 859-870页

作者： Wang Xianlong Zhao Chuan Lin Jincheng Liu Hongxing Zeng Qiuhong Chen Huadong Wang Ye xu Dapeng Chen Wen xu Moping Zhang en Lin Da Lin Zhixiong Sanbo Brain Hospital Capital Medical University Beijing 100093 department of Bioinformatics School of Medical Technology and engineering Key Laboratory of Medical Bioinformatics Key Laboratory of Ministry of Education for Gastrointestinal Cancer Fujian Medical University Fuzhou Fujian 350122 China department of Neurosurgery

Background: Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods: Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results: Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox,P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group (P ening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB (P = 0.01).Conclusions: ACP comprises three molecular subtypes with disti

关键词： Craniopharyngioma Central nervous system tumor Precision medicine beta Catenin Proto-Oncogene Proteins B-raf

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Unraveling the enigma:A comprehensive review of solid pseudopapillary tumor of the pancreas

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 614-629页

作者： Ye-Cheng xu de-Liang Fu Feng Yang department of Pancreatic Surgery Pancreatic Disease InstituteHuashan HospitalFudan UniversityShanghai 200040China

Solid pseudopapillary tumor of the pancreas(SPTP)is a rare neoplasm predom-inantly observed in young females.Pathologically,CTNNB1 mutations,β-catenin nuclear accumulation,and subsequent Wnt-signaling pathway activation are the leading molecular features.Accurate preoperative diagnosis often relies on imaging techniques and endoscopic biopsies.Surgical resection remains the mainstay treatment.Risk models,such as the Fudan Prognostic Index,show promise as predictive tools for assessing the prognosis of SPTP.Establishing three types of metachronous liver metastasis can be beneficial in tailoring individu-alized treatment and follow-up strategies.despite advancements,challenges persist in understanding its etiology,establishing standardized treatments for unresectable or metastatic diseases,and developing a widely recognized grading system.This comprehensive review aims to elucidate the enigma by consolidating current knowledge on the epidemiology,clinical presentation,pathology,molecular characteristics,diagnostic methods,treatment options,and prognostic factors.

关键词： Pancreas Solid pseudopapillary tumor β-catenin endoscopic ultrasound Surgery Recurrence Liver metastasis Prognostic prediction

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Hepatomegaly and jaundice as the presenting symptoms of systemic light-chain amyloidosis: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 550-556页

作者： xu Zhang Fei Tang Yan-Ying Gao de-Zhao Song Jing Liang department of Gastroenterology and Hepatology The Third Central Hospital of TianjinTianjin 300170China Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases Artificial Cell Engineering Technology Research CenterTianjin Institute of Hepatobiliary DiseaseTianjin 300170China department of Interventional Radiology The Third Central Hospital of TianjinTianjin 300170China

BACKGROUND Light chain(AL)amyloidosis is a plasma cell dyscrasia characterized by the pathologic production and extracellular tissue deposition of fibrillar proteins derived from immunoglobulin AL fragments secreted by a clone of plasma cells,which leads to progressive dysfunction of the affected organs.The two most commonly affected organs are the heart and kidneys,and liver is rarely the dominant affected organ with only 3.9%of cases,making them prone to misdia-gnosis and missed diagnosis.CASE SUMMARY A 65-year-old woman was admitted with a 3-mo history of progressive jaundice and marked hepatomegaly.Initially,based on enhanced computed tomography scan and angiography,Budd-Chiari syndrome was considered and balloon dilatation of significant hepatic vein stenoses was performed.However,addi-tional diagnostic procedures,including liver biopsy and bone marrow-exami-nation,revealed immunoglobulin kapa AL amyloidosis with extensive liver involvement and hepatic vascular compression.The disease course was progre-ssive and fatal,and the patient eventually died 5 mo after initial presentation of symptoms.CONCLUSION AL amyloidosis with isolated liver involvement is very rare,and can be easily misdiagnosed as a vascular disease.

关键词： Jaundice Hepatomegaly Liver amyloidosis Kappa light chain Pseudo-Budd-Chiari syndrome Case report

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Prognostic value of a nomogram model for postoperative liver metastasis of colon cancer

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1055-1065页

作者： de-Xin Cheng Kang-Di xu Han-Bo Liu Yi Liu department of Interventional Medicine Zhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina General Surgery Cancer CenterDepartment of Vascular SurgeryZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina

BACKGROUND Colon cancer is one of the most common malignant tumors of the digestive system.Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer.AIM To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery.METHODS We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People’s Hospital from december 2019 to december 2022.Patients were divided into liver metastasis and non-liver metastasis groups.Sex,age,and other general and clinicopathological data(preoperative blood routine and biochemical test indexes)were compared.The risk factors for liver metastasis were analyzed using singlefactor and multifactorial logistic regression.A predictive model was then constructed and evaluated for efficacy.RESULTS Systemic inflammatory index(SII),C-reactive protein/albumin ratio(CAR),red blood cell distribution width(RDW),alanine aminotransferase,preoperative carcinoembryonic antigen level,and lymphatic metastasis were different between groups(Pder the curve was 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively.The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve,with good agreement.The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases,indicating that the model is safer.CONCLUSION Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII,CAR,and RDW.

关键词： Systemic immunoinflammatory index C-reactive protein/albumin ratio Erythrocyte distribution width Colon cancer Liver metastasis Novel nomogram model

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